Genomic and Epigenomic Profile of Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMPs) Revealed Similarities and Differences with Leiomyomas and Leiomyosarcomas.

Donatella Conconi,Patrizia Perego,Marialuisa Lavitrano,Angela Bentivegna,Elena Sala,Andrea Lissoni,Gaia Roversi,Mariachiara Paderno,Serena Redaelli,Fabio Landoni,Chiara Cilibrasi,Eugenio Gautiero,Leda Dalprà

doi:10.3390/ijms22041580

Abstract

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In this work, we analyzed the genomic and epigenomic profile of uterine smooth muscle tumors (USMTs) in order to find similarities and differences between STUMPs, leiomyosarcomas (LMSs) and leiomyomas (LMs), and possibly identify prognostic factors in this group of tumors. Array-CGH data on 23 USMTs demonstrated the presence of a more similar genomic profile between STUMPs and LMSs. Some genes, such as PRKDC and PUM2, with a potential prognostic value, were never previously associated with STUMP. The methylation data appears to be very promising, especially with regards to the divergent profile found in the sample that relapsed, characterized by an overall CGI hypomethylation. Finally, the Gene Ontology analysis highlighted some cancer genes that could play a pivotal role in the unexpected aggressive behavior that can be found in some of these tumors. These genes could prove to be prognostic markers in the future.

Highlights

IntroductionAccording to the 2014 WHO, uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (LM)
We found that 943 unmethylated genes and 180 methylated genes were exclusive to STUMP4, suggesting a specific methylation signature for this tumor
The World Health Organization classifications indicate that uterine smooth muscle tumors that cannot be histologically diagnosed as unequivocally benign or malignant should be termed STUMP [7]

Summary

Introduction

According to the 2014 WHO, uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (LM). Lies a heterogeneous group of rare mesenchymal tumors that cannot be clearly categorized as benign or malignant lesions. Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) do not meet benign variant or true malignancy criteria, due to their variability in histologic appearance, immunohistochemical profile and clinical outcome [1]. The majority of patients with uterine STUMPs have good outcomes, unexpected aggressive behavior can be found in some of the tumors [2]. Because of the neoplasm’s rarity, the etiology, prognostic factors, clinical outcomes and recurrence risks of these tumors are poorly defined [3]. A new classification of lesions according to genomic complexity has been described [4]

Methods

Results

Conclusion